Fungicides dizinyl oxime ethers

ABSTRACT

Fungicidal compounds having the formula (I): ##STR1## and stereoisomers thereof, wherein A is hydrogen, halo, hydroxy, C 1-4  alkyl, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4  haloalkoxy, C 1-4  alkylcarbonyl, C 1-4  alkoxycarbonyl, phenoxy, nitro or cyano; R 1  and R 2 , which may be the same or different, are hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclylalkyl, optionally substituted cycloalkylalkyl, optionally substituted aralkyl, optionally substituted aryloxyalkyl, optionally substituted heterocyclyloxyalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted aryloxy, optionally substituted heterocyclyloxy, nitro halo cyano, --NR 3  R 4 , --CO 2  R 3 , --CONR 3  R 4 , --COR 3 , --S(O) n  R 3  wherein is 0, 1 or 2, (CH 2 ) m  PO(OR 3 ) 2  wherein m is 0 or 1, or R 1  and R 2  join to form a carbocyclic or heterocyclic ring system; R 3  and R 4 , which are the same or different, are hydrogen, optionally substituted alkyl, optionally substituted aralkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or optionally substituted heteroaryl, or R 3  and R 4  join to form an optionally substituted heterocyclic ring; and R 5  and R 6  are independently hydrogen or C 1-4  alkyl.

This is a divisional, of application Ser. No. 07/827,236, filed Jan. 29,1992 now U.S. Pat. No. 5,221,691.

This invention relates to derivatives of O-methyl oxyiminoacetamideuseful as fungicides, insecticides and miticides, to processes forpreparing them, to compositions containing them, and to methods of usingthem to combat fungi, especially fungal infections of plants, and tokill or control insects and mites.

According to the present invention there is provided a compound havingthe formula (I), and stereoisomers thereof, wherein A is hydrogen, halo,hydroxy, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, C₁₋₄alkylcarbonyl, C₁₋₄ alkoxycarbonyl, phenoxy, nitro or cyano; R¹ and R²,which may be the same or different, are hydrogen, optionally substitutedalkyl, optionally substituted cycloalkyl, optionally substitutedheterocyclylalkyl (particularly optionally substituted heteroarylalkyl),optionally substituted cycloalkylalkyl, optionally substituted aralkyl,optionally substituted aryloxyalkyl, optionally substitutedheterocyclyloxyalkyl (particularly optionally substitutedheteroaryloxyalkyl), optionally substituted alkenyl, optionallysubstituted alkynyl, optionally substituted alkoxy, optionallysubstituted aryl, optionally substituted heterocyclyl (particularlyoptionally substituted heteroaryl), optionally substituted aryloxy,optionally substituted heterocyclyloxy (particularly optionallysubstituted heteroaryloxy), nitro, halo, cyano, --NR³ R⁴, --CO₂ R³,--CONR³ R⁴, --COR³, --S(O)_(n) R³ wherein n is 0, 1 or 2, (CH₂)_(m)PO(OR³)₂ wherein m is 0 or 1, or R¹ and R² join to form a carbocyclic orheterocyclic ring system; R³ and R⁴, which are the same or different,are hydrogen, optionally substituted alkyl, optionally substitutedaralkyl, optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted aryl or optionally substituted heteroaryl, or R³and R⁴ join to form an optionally substituted heterocyclic ring; and R⁵and R⁶ are independently hydrogen or C₁₋₄ alkyl.

The compounds of the invention contain at least two carbon-nitrogendouble bonds and are sometimes obtained in the form of mixtures ofgeometric isomers. However these mixtures can be separated intoindividual isomers and this invention embraces such isomers and mixturesthereof in all proportions.

The individual isomers which result from the unsymmetrically substituteddouble bond of the oxime groups are identified by the commonly usedterms "E" and "Z". These terms are defined according to theCahn-Ingold-Prelog system which is fully described in the literature(see, for example, J. March, "Advanced Organic Chemistry", 3rd edition ,Wiley-Interscience, page 109 et seq).

For the carbon-nitrogen double bond of the oxyiminoacetamide group,usually one isomer is more active fungicidally than the other, the moreactive isomer usually being the (E)-isomer. These (E)-isomers form apreferred embodiment of this invention.

Halo includes fluoro, chloro, bromo and iodo.

Alkyl and the alkyl moieties of alkoxy, aralkyl and aryloxyalkyl can bein the form of straight or branched chains and, unless otherwise stated,suitably contain from 1 to 6 carbon atoms. Examples are methyl, ethyl,iso-propyl and tert-butyl. Optional substituents include halo(especially chloro and fluoro), cyano, hydroxy, C₁₋₄ alkoxy and C₁₋₄alkoxy(C₁₋₄)alkoxy. Examples of substituted alkyl and substituted alkoxyare trifluoromethyl and trifluoromethoxy.

Cycloalkyl is suitably C₃₋₆ cycloalkyl, for example cyclopropyl orcyclohexyl, and cycloalkylalkyl is suitably C₃₋₆ cycloalkyl(C₁₋₄)alkyl,for example 1- or 2-cyclopropylethyl. Optional substituents includehalo, hydroxy and C₁₋₄ alkoxy.

Alkenyl and alkynyl suitably contain from 2 to 6 carbon atoms, typically2 to 4 carbon atoms, in the form of straight or branched chains.Examples are ethenyl, allyl and propargyl. Substituted alkenyl andalkynyl groups include optionally substituted aryl- andheteroarylalkenyl (especially optionally substituted aryl- andheteroaryl(C₂₋₄)alkenyl and, particularly, optionally substitutedphenylethenyl) and arylalkynyl.

Aryl and the aryl moieties of aralkyl, arylalkenyl, arylalkynyl, aryloxyand aryloxyalkyl include phenyl and naphthyl.

The carbocyclic or heterocyclic ring system which R¹ and R² may formtogether is suitably a C₄₋₁₀ (typically C₅₋₁₀) aliphatic, aromatic ormixed aliphatic/aromatic carbocyclic ring system, for examplecyclopentyl, cyclohexyl, cyclohexadienonyl and such groups carrying oneor two optionally substituted fused benzene rings and/or substituentssuch as methyl; or it may be a 4- to 10-membered (typically 5- to10-membered) heterocyclic ring system, for example tetrahydropyranyl.

The term heterocyclyl includes aromatic heterocyclic groups, referred toas heteroaryl groups. Heterocyclyl and the heterocyclyl moieties ofother groups, such as heterocyclylalkyl, are typically 5- or 6-memberedaromatic or non-aromatic rings containing one or more O, N or Sheteroatoms which may be fused to one or more other aromatic orheteroaromatic or other heterocyclic rings, such as a benzene ring.Examples are thienyl, furyl, pyrrolyl, isoxazolyl, oxazolyl, pyrazolyl,imidazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, pyrazinyl,pyridazinyl, triazinyl, benzofuryl, benzothienyl, dibenzofuryl,benzothiazolyl, benzoxazolyl, indolyl, quinolinyl and quinoxalinylgroups and, where appropriate, N-oxides thereof.

The optionally substituted heterocyclic ring which R³ and R⁴ may join toform is suitably a 5 to 7 membered hetero ring having 1 to 3 heteroatomswhich are independently selected from O, S or N, and having 1 to 3substituents which are, for example, halogen, cyano, nitro, C₁₋₆ alkyl,C₁₋₆ alkoxy, C₁₋₆ alkylthio, or a heterocyclic ring such as described inthe previous paragraph. Examples are pyrrolidine, piperidine,morpholine, thiomorpholine, piperazine, hexamethyleneimine,tetrahydroquinoline, tetrahydroisoquinoline and2,3-dihydro-1,4-benzoxazine.

Substitutents which may be present in optionally substituted aryl andheterocyclyl, including heteroaryl, moieties include one or more of thefollowing: halo, hydroxy, mercapto, C₁₋₄ alkyl (especially methyl andethyl), C₂₋₄ alkenyl (especially allyl), C₂₋₄ alkynyl (especiallypropargyl), C₁₋₄ alkoxy (especially methoxy), C₂₋₄ alkenyloxy(especially allyloxy), C₂₋₄ alkynyloxy (especially propargyloxy),halo(C₁₋₄)alkyl (especially trifluoromethyl), halo(C₁₋₄)alkoxy(especially trifluoromethoxy), C₁₋₄ alkylthio (especially methylthio),hydroxy(C₁₋₄)alkyl, C₁₋₄ alkoxy(C₁₋₄)alkyl, C₁₋₄ alkoxy(C₁₋₄)alkoxy,C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, optionally substituted aryl(especially optionally substituted phenyl), optionally substitutedheteroaryl (especially optionally substituted pyridyl or pyrimidinyl),optionally substituted aryloxy (especially optionally substitutedphenoxy), optionally substituted heteroaryloxy (especially optionallysubstituted pyridyloxy or pyrimidinyloxy), optionally substitutedaryl(C₁₋₄)alkyl (especially optionally substituted benzyl, optionallysubstituted phenethyl and optionally substituted phenyl n-propyl) inwhich the alkyl moiety is optionally substituted with hydroxy,optionally substituted heteroaryl(C₁₋₄)alkyl (especially optionallysubstituted pyridyl- or pyrimidinyl(C₁₋₄)alkyl), optionally substitutedaryl(C₂₋₄)alkenyl (especially optionally substituted phenylethenyl),optionally substituted heteroaryl(C₂₋₄)alkenyl (especially optionallysubstituted pyridylethenyl or pyrimidinylethenyl), optionallysubstituted aryl(C₁₋₄ )alkoxy (especially optionally substitutedbenzyloxy), optionally substituted heteroaryl(C₁₋₄)alkoxy (especiallyoptionally substituted pyridyl-, or pyrimidinyl(C₁₋₄)alkoxy), optionallysubstituted aryloxy(C₁₋₄)alkyl (especially phenoxymethyl), optionallysubstituted heteroaryloxy(C₁₋₄)alkyl (especially optionally substitutedpyridyloxy- or pyrimidinyloxy(C₁₋₄)alkyl), acyloxy, including C₁₋₄alkanoyloxy (especially acetyloxy) and benzoyloxy, cyano, isocyano,thiocyanato, isothiocyanato, nitro, --NR'R", --NHCOR', --NHCONR'R",--CONR'R", --COOR', --OSO₂ R', --SO₂ R', --COR', --CR'═NR" --N═CR'R" inwhich R' or and R" are independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy,C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl orbenzyl, the phenyl and benzyl groups being optionally substituted withhalogen, C₁₋₄ alkyl or C₁₋₄ alkoxy.

Substituents which may be present in the aryl or heteroaryl rings of anyof the foregoing substituents include one or more of the following:halo, hydroxy, mercapto, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄alkoxy, C₂₋₄ alkenyloxy, C₂₋₄ alkynyloxy, halo(C₁₋₄)alkyl,halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, hydroxy(C₁₋₄)alkyl, C₁₋₄alkoxy(C₁₋₄)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl,alkanoyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato,nitro, --NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --SO₂ R',--OSO₂ R', --COR', --CR'═NR" or --N═CR'R" in which R' and R" have themeanings given above.

In one aspect the invention includes a compound of formula (I) wherein Ais hydrogen, halo, hydroxy, methyl, methoxy, trifluoromethyl,trifluoromethoxy, C₁₋₂ alkylcarbonyl, C₁₋₂ alkoxycarbonyl, phenoxy,nitro or cyano; R¹ is C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy,halo(C₁₋₄)alkoxy, C₁₋₄ alkylcarbonyl, C₁₋₄ alkoxycarbonyl, cyano,phenyl(C₁₋₄)alkyl, phenyl, a 5- or 6-membered aromatic heterocyclecontaining one or more O, N or S atoms and optionally fused to a benzenering, the aromatic or heteroaromatic moieties of any of the foregoingbeing optionally substituted with one or more of halo, hydroxy, C₁₋₄alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄alkylcarbonyl, C₁₋₄ alkoxycarbonyl, nitro, cyano, phenyl, phenoxy,benzyl or benzyloxy; and R² is hydrogen, halo, C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₁₋₄ alkylcarbonyl, C₁₋₄ alkoxycarbonyl, cyano orphenyl; or R¹ and R² join together to form a C₅₋₁₀ carbocyclic ringsystem.

In another aspect the invention includes a compound of formula (I)wherein A is hydrogen or halo; R¹ is C₁₋₄ alkyl, benzyl, C₁₋₄alkylcarbonyl, C₁₋₄ alkoxycarbonyl, cyano, phenyl, thienyl, triazolyl,thiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl,quinolinyl or quinoxalinyl, the aromatic or heteroaromatic moieties ofany of the foregoing being optionally substituted with one or more ofhalo, C₁₋₄ alkyl, trifluoromethyl, C₁₋₄ alkoxy, trifluoromethoxy, nitro,cyano, phenyl or benzyloxy; and R² is hydrogen, C₁₋₄ alkyl, C₁₋₄alkylcarbonyl, C₁₋₄ alkoxycarbonyl, cyano or phenyl; or R¹ and R² jointogether to form a cyclopentyl or cyclohexyl ring to which is optionallyfused a benzene ring; and R⁵ and R⁶ are independently hydrogen or C₁₋₄alkyl.

In yet another aspect the invention includes a compound of formula (I)wherein A is hydrogen; R¹ is phenyl, thienyl, furyl, pyrrolyl,imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl,pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolinyl,quinoxalinyl, benzthiazolyl, benzoxazolyl, benzothienyl or benzofuryl,the aromatic or heteroaromatic moieties of any of the foregoing beingoptionally substituted with one or more of halo, C₁₋₆ alkyl,halo(C₁₋₄)alkyl (especially trifluoromethyl and trifluoroethyl), C₁₋₆alkoxy, cyano(C₁₋₄)alkoxy, halo(C₁₋₄)alkoxy (especiallytrifluoromethoxy), C₁₋₄ alkoxy(C₁₋₄)alkyl, C₁₋₄ alkoxy(C₁₋₄)alkoxy, C₁₋₄alkoxy(C₁₋₄)alkoxy(C₁₋₄)alkoxy, C₁₋₆ alkylthio, C₂₋₆ alkenyl, C₂₋₆alkenyloxy, C₂₋₆ alkynyl, C₂₋₆ alkynyloxy, nitro, cyano, phenyl,phenoxy, benzyloxy, CO₂ R', CONR'R", CSNR'R", NR'R", S(O)_(n) R',NHCONR'R", in which R' and R" are independently H or C₁₋₄ alkyl and n is0, 1 or 2; R² is methyl; R⁵ is hydrogen and R⁶ is methyl; or, whereappropriate, the N-oxide thereof.

This invention is illustrated by the compounds listed in Tables I, IIand III which follow. Throughout the Tables the O-methyloxyiminoacetamide group has the (E)-configuration.

Table I consists of 350 compounds of formula (I.1) in which the valuesof R¹, R² and A are given in the Table.

                                      TABLE I                                     __________________________________________________________________________    Compound                                                                      No.    R.sup.1            R.sup.2     A                                       __________________________________________________________________________     1     2-CH.sub.3 O--C.sub.6 H.sub.4                                                                    H           H                                        2     3-CH.sub.3 O--C.sub.6 H.sub.4                                                                    H           H                                        3     4-CH.sub.3 O--C.sub.6 H.sub.4                                                                    H           H                                        4     2-CH.sub.3 --C.sub.6 H.sub.4                                                                     H           H                                        5     3-CH.sub.3 --C.sub.6 H.sub.4                                                                     H           H                                        6     4-CH.sub.3 --C.sub.6 H.sub.4                                                                     H           H                                        7     2-F--C.sub.6 H.sub.4                                                                             H           H                                        8     3-F--C.sub.6 H.sub.4                                                                             H           H                                        9     4-F--C.sub.6 H.sub.4                                                                             H           H                                        10    2-Cl--C.sub.6 H.sub.4                                                                            H           H                                        11    3-Cl--C.sub.6 H.sub.4                                                                            H           H                                        12    4-Cl--C.sub.6 H.sub.4                                                                            H           H                                        13    2-Br--C.sub.6 H.sub.4                                                                            H           H                                        14    3-Br--C.sub.6 H.sub.4                                                                            H           H                                        15    4-Br--C.sub.6 H.sub.4                                                                            H           H                                        16    2-NO.sub.2 --C.sub.6 H.sub.4                                                                     H           H                                        17    3-NO.sub.2 --C.sub.6 H.sub.4                                                                     H           H                                        18    4-NO.sub.2 --C.sub.6 H.sub. 4                                                                    H           H                                        19    2-CF.sub.3 --C.sub.6 H.sub.4                                                                     H           H                                        20    3-CF.sub.3 --C.sub.6 H.sub.4                                                                     H           H                                        21    4-CF.sub.3 --C.sub.6 H.sub.4                                                                     H           H                                        22    C.sub.6 H.sub.5    H           H                                        23    C.sub.6 H.sub.5    CH.sub.3    H                                        24    C.sub.6 H.sub.5    C.sub.6 H.sub.5                                                                           H                                        25    2-C.sub.6 H.sub.5 --C.sub.6 H.sub.4                                                              H           H                                        26    3-C.sub.6 H.sub.5 --C.sub.6 H.sub.4                                                              H           H                                        27    4-C.sub.6 H.sub.5 --C.sub.6 H.sub.4                                                              H           H                                        28    2-(C.sub.6 H.sub.5 CH.sub.2 O)--C.sub.6 H.sub.4                                                  H           H                                        29    3-(C.sub.6 H.sub.5 CH.sub.2 O)--C.sub.6 H.sub.4                                                  H           H                                        30    4-(C.sub.6 H.sub.5 CH.sub.2 O)--C.sub.6 H.sub.4                                                  H           H                                        31    2-cyano-C.sub.6 H.sub.4                                                                          H           H                                        32    3-cyano-C.sub.6 H.sub.4                                                                          H           H                                        33    4-cyano-C.sub.6 H.sub.4                                                                          H           H                                        34    2-CF.sub.3 O--C.sub.6 H.sub.4                                                                    H           H                                        35    3-CF.sub.3 O--C.sub.6 H.sub.4                                                                    H           H                                        36    4-CF.sub.3 O--C.sub. 6 H.sub.4                                                                   H           H                                        37    pyrid-2-yl         H           H                                        38    pyrid-3-yl         H           H                                        39    pyrid-4-yl         H           H                                        40    pyrid-2-yl         CH.sub.3    H                                        41    pyrid-2-yl         cyano       H                                        42    pyrid-2-yl         CO.sub.2 C.sub.2 H.sub.5                                                                  H                                        43    pyrid-2-yl         CO.sub.2 CH.sub.3                                                                         H                                        44    pyrimidin-2-yl     H           H                                        45    pyrimidin-4-yl     H           H                                        46    thien-2-yl         H           H                                        47    thien-2-yl         CH.sub.3    H                                        48    5-Cl-thien-2-yl    H           H                                        49    CO.sub.2 C.sub.2 H.sub.5                                                                         CO.sub.2 C.sub.2 H.sub.5                                                                  H                                        50    CO.sub.2 CH.sub.3  CO.sub.2 CH.sub.3                                                                         H                                        51    COCH.sub.3         COCH.sub.3  H                                        52    cyano              cyano       H                                        53    .0.                .0.         H                                        54    .0.                .0.         H                                        55    .0.                .0.         H                                        56    tert-C.sub.4 H.sub.9                                                                             H           H                                        57    C.sub.6 H.sub.5 CH.sub.2                                                                         H           H                                        58    2,4-di-Cl--C.sub.6 H.sub.3                                                                       H           H                                        59    2,4-di-F-C.sub.6 H.sub.3                                                                         H           H                                        60    3,5-di-CH.sub.3 --C.sub.6 H.sub.3                                                                H           H                                        61    3,5-di-CH.sub.3 O--C.sub.6 H.sub.3                                                               H           H                                        62    pyrazin-2-yl       CH.sub.3    H                                        63    6-CH.sub.3 -pyrid-3-yl                                                                           CH.sub.3    H                                        64    pyrid-2-yl         C.sub.2 H.sub.5                                                                           H                                        65    pyrid-3-yl         CH.sub.3    H                                        66    pyrimidin-5-yl     iso-C.sub.3 H.sub.7                                                                       H                                        67    iso-C.sub.3 H.sub.7                                                                              pyrimidin-5-yl                                                                            H                                        68    pyrid-4-yl         CH.sub.3    H                                        69    6-Cl-pyrid-2-yl    CH.sub.3    H                                        70    5-Cl-pyrid-2-yl    CH.sub.3    H                                        71    4-Cl-pyrid-2-yl    CH.sub.3    H                                        72    3-Cl-pyrid-2-yl    CH.sub.3    H                                        73    6-cyano-pyrid-2-yl CH.sub.3    H                                        74    5-cyano-pyrid-2-yl CH.sub.3    H                                        75    4-cyano-pyrid-2-yl CH.sub.3    H                                        76    3-cyano-pyrid-2-yl CH.sub.3    H                                        77    6-Br-pyrid-2-yl    CH.sub.3    H                                        78    5-Br-pyrid-2-yl    CH.sub.3    H                                        79    4-Br-pyrid-2-yl    CH.sub.3    H                                        80    3-Br-pyrid-2-yl    CH.sub.3    H                                        81    6-CH.sub.3 -pyrid-2-yl                                                                           CH.sub.3    H                                        82    5-CH.sub.3 -pyrid-2-yl                                                                           CH.sub.3    H                                        83    4-CH.sub.3 -pyrid-2-yl                                                                           CH.sub.3    H                                        84    3-CH.sub.3 -pyrid-2-yl                                                                           CH.sub.3    H                                        85    6-F-pyrid-2-yl     CH.sub.3    H                                        86    5-F-pyrid-2-yl     CH.sub.3    H                                        87    4-F-pyrid-2-yl     CH.sub.3    H                                        88    3-F-pyrid-2-yl     CH.sub.3    H                                        89    3-CH.sub.3 -pyrazin-2-yl                                                                         CH.sub.3    H                                        90    3-C.sub.2 H.sub.5 -pyrazin-2-yl                                                                  CH.sub.3    H                                        91    3-Cl-pyrazin-2-yl  CH.sub.3    H                                        92    3-OCH.sub.3 -pyrazin-2-yl                                                                        CH.sub. 3   H                                        93    5-CO.sub.2 CH.sub.3 -pyrazin-2-yl                                                                CH.sub.3    H                                        94    5-CO.sub.2 C.sub.2 H.sub.5 pyrazin-2-yl                                                          CH.sub.3    H                                        95    3-cyano-pyrazin-2-yl                                                                             CH.sub.3    H                                        96    pyrimidin-4-yl     CH.sub.3    H                                        97    2-Cl-pyrimidin-4-yl                                                                              CH.sub.3    H                                        98    2-OCH.sub.3 -pyrimidin-4-yl                                                                      CH.sub.3    H                                        99    2-CH.sub.3 -pyrimidin-4-yl                                                                       CH.sub.3    H                                       100    2-cyano-pyrimidin-4-yl                                                                           CH.sub.3    H                                       101    thiazol-2-yl       CH.sub.3    H                                       102    thien-3-yl         CH.sub.3    H                                       103    5-Cl-thien-2-yl    CH.sub.3    H                                       104    5-CH.sub.3 -thien-2-yl                                                                           CH.sub.3    H                                       105    5-Br-thien-2-yl    CH.sub.3    H                                       106    5-cyano-thien-2-yl CH.sub.3    H                                       107    3-CH.sub.3 -thien-2-yl                                                                           CH.sub.3    H                                       108    2-OCH.sub.3 --C.sub.6 H.sub.4                                                                    CH.sub.3    H                                       109    3-OCH.sub.3 --C.sub.6 H.sub.4                                                                    CH.sub.3    H                                       110    4-OCH.sub.3 --C.sub.6 H.sub.4                                                                    CH.sub.3    H                                       111    2-CH.sub.3 --C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       112    3-CH.sub.3 --C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       113    4-CH.sub.3 --C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       114    2-F--C.sub.6 H.sub.4                                                                             CH.sub.3    H                                       115    3-F--C.sub.6 H.sub.4                                                                             CH.sub.3    H                                       116    4-F--C.sub.6 H.sub.4                                                                             CH.sub.3    H                                       117    2-Cl--C.sub.6 H.sub. 4                                                                           CH.sub.3    H                                       118    3-Cl--C.sub.6 H.sub.4                                                                            CH.sub.3    H                                       119    4-Cl--C.sub.6 H.sub.4                                                                            CH.sub.3    H                                       120    2-Br--C.sub.6 H.sub.4                                                                            CH.sub.3    H                                       121    3-Br--C.sub.6 H.sub.4                                                                            CH.sub.3    H                                       122    4-Br--C.sub.6 H.sub.4                                                                            CH.sub.3    H                                       123    2-NO.sub.2 --C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       124    3-NO.sub.2 --C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       125    4-NO.sub.2 --C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       126    2-CF.sub.3 --C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       *127   3-CF.sub.3 --C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       128    4-CF.sub.3 --C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       129    2-cyano-C.sub.6 H.sub.4                                                                          CH.sub.3    H                                       130    3-cyano-C.sub.6 H.sub.4                                                                          CH.sub.3    H                                       131    4-cyano-C.sub.6 H.sub.4                                                                          CH.sub.3    H                                       132    3,4,5-(OCH.sub.3).sub.3 --C.sub.6 H.sub.2                                                        CH.sub.3    H                                       133    3,5-di-F-pyrid-2-yl                                                                              CH.sub.3    H                                       134    3,4,5,6-F.sub.4 -pyrid-2-yl                                                                      CH.sub.3    H                                       135    2,6-di-Cl-pyrid-3-yl                                                                             CH.sub.3    H                                       136    pyridazin-3-yl     CH.sub.3    H                                       137    pyridazin-4-yl     CH.sub.3    H                                       138    6-CH.sub.3 -pyridazin-3-yl                                                                       CH.sub.3    H                                       139    4-cyano-quinolin-2-yl                                                                            CH.sub.3    H                                       140    quinoxalin-2-yl    CH.sub.3    H                                       141    C.sub.6 H.sub.5    CH.sub.3    6-F                                     142    C.sub.6 H.sub.5    CH.sub.3    6-Cl                                    143    6-CH.sub.3 -pyrimidin-4-yl                                                                       CH.sub.3    H                                       144    4-CH.sub.3 -pyrimidin-5-yl                                                                       CH.sub.3    H                                       145    4-CH.sub.3 -pyrimidin-2-yl                                                                       CH.sub.3    H                                       146    4,6-di-CH.sub.3 -pyrimidin-2-yl                                                                  CH.sub.3    H                                       147    2,6-di-CH.sub.3 -pyrimidin-4-yl                                                                  CH.sub.3    H                                       148    2,4-di-CH.sub.3 -pyrimidin-5-yl                                                                  CH.sub.3    H                                       149    6-Cl-pyrimidin-4-yl                                                                              CH.sub.3    H                                       150    6-OCH.sub.3 -pyrimidin-4-yl                                                                      CH.sub.3    H                                       151    4,6-di-OCH.sub.3 -pyrimidin-2-yl                                                                 CH.sub.3    H                                       152    .0.                .0.         H                                       153    .0.                .0.         H                                       154     .sub.--N-oxide-pyrid-2-yl                                                                       CH.sub.3    H                                       155    5-C.sub.2 H.sub.5 -pyrid-2-yl                                                                    CH.sub.3    H                                       156    CH.sub.3 CO        CH.sub.3    H                                       157    C.sub.6 H.sub.5 CO CH.sub.3    H                                       158     .sub.--N--CH.sub.3 -pyrrol-2-yl                                                                 CH.sub.3    H                                       159    4-Cl-quinolin-2-yl CH.sub.3    H                                       160    2,4-di-Cl--C.sub.6 H.sub.3                                                                       1,2,4-tri-  H                                                                 azol-1-yl-CH.sub.2                                  161    2,4-di-Cl--C.sub.6 H.sub.3                                                                       pyrid-3-yl-CH.sub.2                                                                       H                                       162    2,4-di-CH.sub.3 -thiazol-5-yl                                                                    CH.sub.3    H                                       163    furan-2-yl         CH.sub.3    H                                       164    2,4-di-CH.sub.3 -furan-3-yl                                                                      CH.sub.3    H                                       165    pyrid-2-yl         pyrid-2-yl  H                                       166    6-C.sub.6 H.sub.5 -pyrimidin-4-yl                                                                CH.sub.3    H                                       167    4-cyano-pyrid-3-yl CH.sub.3    H                                       168    1,2,4-triazin-5-yl CH.sub. 3   H                                       169    3-CH.sub.3 -1,2,4-triazin-5-yl                                                                   CH.sub.3    H                                       170    3-C.sub.6 H.sub.5 -1,2,4-triazin-5-yl                                                            CH.sub.3    H                                       171    3-SCH.sub.3 -1,2,4-triazin-5-yl                                                                  CH.sub.3    H                                       172    3-OCH.sub.3 -1,2,4-triazin-5-yl                                                                  CH.sub.3    H                                       173    5-CONH.sub.2 -pyrazin-2-yl                                                                       CH.sub.3    H                                       174    5-cyano-pyrazin-2-yl                                                                             CH.sub.3    H                                       175    5,6-di-CH.sub.3 -pyrazin-2-yl                                                                    CH.sub.3    H                                       176    3,5-di-CH.sub.3 -pyrazin-2-yl                                                                    CH.sub.3    H                                       177    3,6-di-CH.sub.3 -pyrazin-2-yl                                                                    CH.sub.3    H                                       178    5-CH.sub.3 -pyrazin-2-yl                                                                         CH.sub.3    H                                       179    6-CH.sub.3 -pyrazin-2-yl                                                                         CH.sub.3    H                                       180    5-Cl-pyrazin-2-yl  CH.sub.3    H                                       181    6-Cl-pyrazin-2-yl  CH.sub.3    H                                       182    5,6-dicyano-pyrazin-2-yl                                                                         CH.sub.3    H                                       183    4-SO.sub.2 CH.sub.3 --C.sub.6 H.sub.4                                                            CH.sub.3    H                                       184    4-NH.sub.2 --C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       185    2,4-di-Cl--C.sub.6 H.sub.3                                                                       CH.sub.3    H                                       186    2,4-di-CH.sub.3 --C.sub.6 H.sub.3                                                                CH.sub.3    H                                       187    4-NHCONH.sub.2 --C.sub.6 H.sub.4                                                                 CH.sub.3    H                                       188    C.sub.6 H.sub.5    cyclopropyl H                                       189    C.sub.6 H.sub.5    Cl          H                                       190    4-C.sub.2 H.sub.5 O--C.sub.6 H.sub.4                                                             CF.sub.3    H                                       191    C.sub.6 H.sub.5    SCH.sub.3   H                                       192    C.sub.6 H.sub.5    F           H                                       193    C.sub.6 H.sub.5    OC.sub.2 H.sub.5                                                                          H                                       194    C(CH.sub.3).sub.3  CH.sub.3    H                                       195    cyclohexyl-CH.sub.2                                                                              CH.sub.3    H                                       196    C.sub.6 H.sub.5 --CH.sub.2                                                                       CH.sub.3    H                                       197    pyrazin-2-yl-CH.sub.2                                                                            CH.sub.3    H                                       198    ( .sub.--E)-C.sub.6 H.sub.5 --CH═CH                                                          CH.sub.3    H                                       199    C.sub.6 H.sub.5    CH.sub.3    H                                       200    C.sub.6 H.sub.5    CH.sub.2 Cl H                                       201    benzthiazol-2-yl   CH.sub.3    H                                       202    benzoxazol-2-yl    CH.sub.3    H                                       203    pyrazin-2-yl       C.sub.2 H.sub.5                                                                           H                                       204    5-OCH.sub.3 -pyrazin-2-yl                                                                        CH.sub.3    H                                       205    6-OCH.sub.3 -pyrazin-2-yl                                                                        CH.sub.3    H                                       206    6-cyano-pyrazin-2-yl                                                                             CH.sub.3    H                                       207    5-cyano-pyrid-3-yl CH.sub.3    H                                       208    6-cyano-pyrid-3-yl CH.sub.3    H                                       209    3-cyano-pyrid-4-yl CH.sub.3    H                                       210    2-cyano-pyrid-4-yl CH.sub.3    H                                       211    pyrimidin-5-yl     CH.sub.3    H                                       212    2-CH.sub.3 -pyrimidin-5-yl                                                                       CH.sub.3    H                                       213    3-OCH.sub.3 -isoxazol-5-yl                                                                       CH.sub.3    H                                       214    3-Br-isoxazol-5-yl CH.sub.3    H                                       215    5-NO.sub.2 -thiazol-2-yl                                                                         CH.sub.3    H                                       216    5-CH.sub.3 -thiazol-2-yl                                                                         CH.sub.3    H                                       217    4-CH.sub.3 -thiazol-5-yl                                                                         CH.sub.3                                            218    2-Cl,4-CH.sub.3 -thiazol-5-yl                                                                    CH.sub.3    H                                       219    3,5-di-OCH.sub.3 -1,2,4-                                                                         CH.sub.3    H                                              triazin-6-yl                                                           220    3,6-di-CH.sub.3 -pyridazin-4-yl                                                                  CH.sub.3    H                                       221    2-(C.sub.6 H.sub.5 O)--C.sub.6 H.sub.4                                                           CH.sub.3    H                                       222    3-(C.sub.6 H.sub.5 O)--C.sub.6 H.sub.4                                                           CH.sub.3    H                                       223    4-(C.sub.6 H.sub.5)--C.sub.6 H.sub.4                                                             CH.sub.3    H                                       224    1,2,4-triazol-1-yl-CH.sub.2                                                                      CH.sub.3    H                                       225    C.sub.6 H.sub.5    OCH.sub.3   H                                       226    OCH.sub.3          C.sub.6 H.sub.5                                                                           H                                       227    C.sub.6 H.sub.5    CH.sub.3 S(O)                                                                             H                                       228    C.sub.6 H.sub.5    CH.sub.3 S(O)                                                                             H                                       229    C.sub.6 H.sub.5    N(CH.sub.3).sub.2                                                                         H                                       230    C.sub.6 H.sub.5 O  CH.sub.3    H                                       231    C.sub.6 H.sub.5    Br          H                                       232    C.sub.6 H.sub.5    I           H                                       233    C.sub.6 H.sub.5    (CH.sub.3).sub.2 CHS                                                                      H                                       234    Pyrimidin-2-yl     CH.sub.3 O  H                                       235    Pyrazin-2-yl       Cl          H                                       236    3-OC.sub.2 H.sub.5 -pyrazin-2-yl                                                                 CH.sub.3    H                                       237    pyrid-2-yl         SCH.sub.3   H                                       238    pyrid-2-yl         SO.sub.2 CH.sub.3                                                                         H                                       239    Pyrid-2-yl         SOCH.sub.3  H                                       240    3,5-di-CH.sub.3 -oxazol-4-yl                                                                     CH.sub.3    H                                       241    pyrid-2-yl         OCH.sub.3   H                                       242    pyrid-2-yl         SC.sub.2 H.sub.5                                                                          H                                       243    pyrid-2-yl         OC.sub.6 H.sub.5                                                                          H                                       244    pyrid-2-yl         OCH.sub.2 --C.sub.6 H.sub.5                                                               H                                       245    6-OC.sub.2 H.sub.5 -pyrimidin-4-yl                                                               CH.sub.3    H                                       246    pyrid-2-yl         NH.sub.2    H                                       247    SCH.sub.3          pyrid-2-yl  H                                       248    2,4-di-F--C.sub.6 H.sub.3                                                                        CH.sub.3    H                                       249    2,4-di-OCH.sub.3 --C.sub.6 H.sub.3                                                               CH.sub.3    H                                       250    5-CH.sub.3 -pyrimidin-2-yl                                                                       CH.sub.3    H                                       251    SO.sub.2 CH.sub.3  pyrid-2-yl  H                                       252    pyrid-3-yl         SCH.sub.3   H                                       253    pyrid-3-yl         OCH.sub.3   H                                       254    6-CF.sub.3 -pyrid-2-yl                                                                           CH.sub.3    H                                       255    3-CF.sub.3 -4-F--C.sub.6 H.sub.3                                                                 CH.sub.3    H                                       256    6-CF.sub.3 -pyrimidin-4-yl                                                                       CH.sub.3    H                                       257    3,5-di-F--C.sub.6 H.sub.3                                                                        CH.sub.3    H                                       258    2-CH.sub.3 CH.sub.2 S-pyrimidin-4-yl                                                             CH.sub.3    H                                       259    2-CF.sub.3 -pyrimidin-4-yl                                                                       CH.sub.3    H                                       260    4-CF.sub.3 -pyrid-2-yl                                                                           CH.sub.3    H                                       261    2-phenyl-thiazol-4-yl                                                                            CH.sub.3    H                                       262    3-NH.sub.2 C(O)--C.sub.6 H.sub.4                                                                 CH.sub.3    H                                       263    4-CF.sub.3 -pyrimidin-2-yl                                                                       CH.sub.3    H                                       264    3,5-di-CF.sub.3 --C.sub.6 H.sub.3                                                                CH.sub.3    H                                       265    2-(2-CN--C.sub.6 H.sub.4 --O-)-pyrimidin-                                                        CH.sub.3    H                                              4-yl                                                                   266    3- "n-C.sub.3 H.sub.7 O--C.sub.6 H.sub.4                                                         CH.sub.3    H                                       267    2-CH(CH.sub.3).sub.2 --O-pyrimidin-4-yl                                                          CH.sub.3    H                                       268    6-CF.sub.3 -pyrazin-2-yl                                                                         CH.sub.3    H                                       269    4-C.sub.2 H.sub.5 O-pyrimidin-2-yl                                                               CH.sub.3    H                                       270    6-C.sub.2 F.sub.5 -pyrimidin-4-yl                                                                CH.sub. 3   H                                       271    3-CF.sub.3 O--C.sub.6 H.sub.4                                                                    CH.sub.3    H                                       272    4-CH.sub.3 O-pyrid-2-yl                                                                          CH.sub.3    H                                       273    2-propargyloxy-pyrimidin-4-yl                                                                    CH.sub.3    H                                       274    2-C.sub.2 H.sub.5 O-pyrimidin-4-yl                                                               CH.sub.3    H                                       275    2-allyloxy-pyrimidin-4-yl                                                                        CH.sub.3    H                                       276    3-CH.sub.3 O-pyridazin-6-yl                                                                      CH.sub.3    H                                       277    3-C.sub.2 H.sub.5 O-pyridazin-6-yl                                                               CH.sub.3    H                                       278    3-allyloxy-C.sub.6 H.sub.4                                                                       CH.sub.3    H                                       279    4-CH.sub.3 S-pyrimidin-2-yl                                                                      CH.sub.3    H                                       280    4-CH.sub.3 O-pyrimidin-2-yl                                                                      CH.sub.3    H                                       281    3-CF.sub.3 --C.sub.6 H.sub.4                                                                     SCH.sub.3   H                                       282    3-CF.sub.3 --C.sub.6 H.sub.4                                                                     CF.sub.3    H                                       283    3-CF.sub.3 --C.sub.6 H.sub.4                                                                     C.sub.2 H.sub.5                                                                           H                                       284    3-CF.sub.3 --C.sub.6 H.sub.4                                                                     NH.sub.2    H                                       285    3-CF.sub.3 --C.sub.6 H.sub.4                                                                     imidazolyl  H                                       286    3-CF.sub.3 --C.sub.6 H.sub.4                                                                     N(CH.sub.3).sub.2                                                                         H                                       287    3-CF.sub.3 --C.sub.6 H.sub.4                                                                     NHCH.sub.3  H                                       288    PO(OC.sub.2 H.sub.5).sub.2                                                                       CH.sub.3    H                                       289    PO(OC.sub.2 H.sub.5).sub.2                                                                       C.sub.6 H.sub.5                                                                           H                                       290    4-CH.sub.3 O-6-(CO.sub.2 CH.sub.3)-pyrimidin-2-yl                                                CH.sub.3    H                                       291    pyrrol-2-yl        CH.sub.3    H                                       292    CH.sub.3           pyrrol-2-yl H                                       293    5-CF.sub.3 -pyrid-3-yl                                                                           CH.sub.3    H                                       294    3-(pyrimidinyloxy)-C.sub.6 H.sub.4                                                               CH.sub.3    H                                       295    3-propargyloxy-C.sub.6 H.sub.4                                                                   CH.sub.3    H                                       296    CH.sub.3           H           H                                       297    5-(2,4-difluorophenyl)-furan-2-yl                                                                CH.sub.3    H                                       298    CH.sub.3           5-(2,4-difluorophenyl)-                                                                   H                                                                 furan-2-yl                                          299    C.sub.2 H.sub.5 O  CH.sub.3    H                                       300    4-tert-butyl-C.sub.6 H.sub.4                                                                     CH.sub.3    H                                       301    4-propargyloxy-pyrimidin-2-yl                                                                    CH.sub.3    H                                       302    2-C.sub.2 H.sub.5 O--C.sub.6 H.sub.4                                                             CH.sub.3    H                                       303    4-C.sub.2 H.sub.5 --C.sub.6 H.sub.4                                                              CH.sub.3    H                                       304    3-C.sub.2 H.sub.5 O--C.sub.6 H.sub.4                                                             CH.sub.3    H                                       305    CH.sub.3 S         CH.sub.3    H                                       306    CH.sub.3 SO.sub.2  CH.sub.3    H                                       307    .0.                .0.         H                                       308    4- "n-C.sub.3 H.sub.7 O-pyrimidin-2-yl                                                           CH.sub.3    H                                       309    3- "n-hexyloxy-C.sub.6 H.sub.4                                                                   CH.sub.3    H                                       310    4- "n-butyloxy-pyrimidin-2-yl                                                                    CH.sub.3    H                                       311    benzothiophen-3-yl CH.sub.3    H                                       312    3-[(CH.sub.3).sub.2 C═CHCH.sub.2 O]--C.sub.6 H.sub.4                                         CH.sub.3    H                                       313    2,4-di-CH.sub.3 O-pyrimidin-6-yl                                                                 CH.sub.3    H                                       314    3-CF.sub.3 --C.sub.6 H.sub.4                                                                     1,2,4-triazol-1-yl                                                                        H                                       315    3-CH.sub.3 S-pyrazin-2-yl                                                                        CH.sub.3    H                                       316    3-N(CH.sub.3)S-pyrazin-2-yl                                                                      CH.sub.3    H                                       317    3-CF.sub.3 --C.sub.6 H.sub.4                                                                     Cl          H                                       318    .0.                .0.         H                                       319    benzofuran-2-yl    CH.sub.3    H                                       320    2-CH.sub.3 S(O)-pyrimidin-4-yl                                                                   CH.sub.3    H                                       321    3-NH.sub.2 C(S)--C.sub.6 H.sub.4                                                                 CH.sub.3    H                                       322    4-NH.sub.2 C(S)-pyrid-2-yl                                                                       CH.sub.33   H                                       323    3-(CH.sub.3 OCH.sub.2 CH.sub.2 OCH.sub.2 O)--C.sub.6 H.sub.4                                     CH.sub.3    H                                       324    3-(cyanomethoxy)-C.sub.6 H.sub.4                                                                 CH.sub.3    H                                       325    .0.                .0.         H                                       326    3-(F.sub.2 HCO)--C.sub.6 H.sub.4                                                                 CH.sub.3    H                                       327    6-C.sub.2 H.sub.5 O-pyrazin-2-yl                                                                 CH.sub.3    H                                       328    4-CH.sub.3 -6-OCH.sub.3 -pyrimidin-2-yl                                                          CH.sub.3    H                                       329    4-CH.sub.3 -thien-2-yl                                                                           CH.sub.3    H                                       330    2,4-di-CH.sub.3 -thiazol-5-yl                                                                    CH.sub.3    H                                       331    4-CF.sub.3 -6-CH.sub.3 -pyrimidin-2-yl                                                           CH.sub.3    H                                       332    5-Br-pyrid-3-yl    CH.sub.3    H                                       333    5-CONHCH.sub.3 -pyrazin-2-yl                                                                     CH.sub.3    H                                       334    4,6-di-OC.sub.2 H.sub.5 -pyrimidin-2-yl                                                          CH.sub.3    H                                       +335   5-CH.sub.3 -furan-2-yl                                                                           CH.sub.3    H                                       +335A  5-CH.sub.3 -furan-2-yl                                                                           CH.sub.3    H                                       336    2-SCH.sub.3 -pyrimidin-4-yl                                                                      CH.sub.3    H                                       337    4-iso-C.sub.3 H.sub.7 O-pyrimidin-2-yl                                                           CH.sub.3    H                                       338      .sub.--N-CH.sub.3 -3-CH.sub.3 -5-OC.sub.6 H.sub.5 -pyrazol-4-yl                                H           H                                       339    3-CH.sub.3 -benzothiophen-2-yl                                                                   CH.sub.3    H                                       340    4-OCH.sub.2 CF.sub.3 -pyrimidin-2-yl                                                             CH.sub.3    H                                       341    2-N(CH.sub.3).sub.2 -pyrimidin-4-yl                                                              CH.sub.3    H                                       342    5-NO.sub.2 -pyrid-2-yl                                                                           CH.sub.3    H                                       343    2-tert-C.sub.4 H.sub.9 -pyrimidin-5-yl                                                           CH.sub.3    H                                       344    5-NO.sub.2 -benzofuran-2-yl                                                                      CH.sub.3    H                                       345    4-O(CH.sub.2).sub.2 OCH.sub.3 -pyrid-2-yl                                                        CH.sub.3    H                                       346    3,4-di-Cl--C.sub.6 H.sub.3                                                                       CH.sub.3    H                                       347    6-OC.sub.2 H.sub.5 -pyrid-2-yl                                                                   CH.sub.3    H                                       348    4-CF.sub.3 -6-OCH.sub.2 CF.sub.3 -pyrid-2-yl                                                     CH.sub.3    H                                       349    4-CF.sub.3 -6-OC.sub.2 H.sub.5 -pyrid-2-yl                                                       CH.sub.3    H                                       340    5-CF.sub.3 -pyrid-2-yl                                                                           CH.sub.3    H                                       __________________________________________________________________________     Key                                                                           *For a preparation of this compound, see Example 1.                           + Compound 335 is one isomer and Compound 335A is a 2:1 mixture of two        isomers.                                                                      .0. Groups R.sup.1 and R.sup.2 join to form a ring as shown under             `Chemical Formulae` later.                                               

Table II consists of 350 compounds of the formula (I.2). The values ofR¹, R² and A of each compound correspond to the values given for thecompound of the same number in Table I. The only difference between thecompounds of Table I and Table II is that the compounds of Table I havea single N-methyl substituent on the acetamide group, whereas thecompounds of Table II have two N-methyl substituents on the acetamidegroup.

Table III consists of 350 compounds of the formula (I.3). The values ofR¹, R² and A of each compound correspond to the values given for thecompound of the same number in Table I. The only difference between thecompounds of Table I and Table III is that the compounds of Table I havean N-methyl substituent on the acetamide group, whereas the compounds ofTable III have no N-substituents on the acetamide group.

                                      TABLE IV                                    __________________________________________________________________________    Table IV gives melting points or selected proton NMR data obtained at         270 MHz for certain compounds described in Table I and for compound No.       346                                                                           in Table III. Chemical shifts are measured at 20° C. in ppm from       tetramethylsilane and deuterchloroform was used as solvent, unless            otherwise stated. The following abbreviations are used:                       s = singlet     m = multiplet                                                                             d = doublet                                       dd = double doublet                                                                           t = triplet br = broad                                        ppm = parts per million                                                       Compound                                                                      No                                                                            Table I                                                                             Melting                                                                 except as                                                                           Point                                                                   shown)                                                                              (°C.)                                                                        Proton NMR Data (δ)                                         __________________________________________________________________________     40   Gum   2.30(3H, s), 2.88(3H, d), 3.94(3H, s), 5.14(2H, s),                           6.72(1H, br), 7.16-7.25(2H, m), 7.32-7.43(2H, m),                             7.48-7.51(1H, m), 7.60-7.68(1H, m), 7.81-7.85(1H, d),                         8.58-8.60(1H, d) ppm.                                              47   77-79                                                                    63   92-94                                                                    75   Gum   2.28(3H, s), 2.9(3H, d), 3.95(3H, s), 5.18(2H, s),                            6.8(1H, br), 7.18-7.21(1H, m), 7.31-7.51(4H, m),                              8.12(1H, s), 8.70(1H, d) ppm.                                     103   70-71                                                                   109   53-55                                                                   113   62-64                                                                   115   Gum   2.18(3H, s), 2.88(3H, d), 3.95(3H, s), 5.12(2H, s),                           6.73(1H, br), 6.99-7.07(1H, m), 7.17-7.22(1H, m),                             7.28-7.52(6H, m) ppm.                                             127   Gum   2.22(3H, s), 2.88(3H, d), 3.94(3H, s), 5.14(2H, s),                           6.74(1H, br m), 7.1-7.9(8H, m) ppm                                158   76-78                                                                   176   Gum   2.2(3H, s), 2.5(6H, s), 2.95(3H, d), 3.95(3H, s),                             5.1(2H, s), 6.75(1H, m), 7.1-7.5(4H, m), 8.25(1H, s) ppm.         188   105-107                                                                 194   71-73                                                                   198   88-90                                                                   236    99-100                                                                 260   120.8-122                                                               264   138-140                                                                 269     121-122.5                                                             295   103-105                                                                 326   41-43                                                                   328   89-91                                                                   329   73-75                                                                   330   122-124                                                                 331   161-163                                                                 332   112-113                                                                 333   140-142                                                                 334   93-95                                                                   335   108-109                                                                 335A  Gum   2:1 mixture of isomers, Major component:                                      2.18(3H, s), 2.32(3H, s), 2.8(3H, d), 3.92(3H, s),                            5.06(2H, s), 6.07(1H, d), 6.64(1H, br), 7.03(1H, m),                          7.17-7.23(1H, m), 7.33-7.45(2H, m), 7.47-7.53(1H, m)                          ppm.                                                                          Minor component:                                                              2.08(s), 2.34(s), 2.9(d), 3.94(s), 5.11(s), 6.02(d),                          6.49(d), 6.72(br), 7.17-7.23(m), 7.33-7.45(m),                                7.47-7.52(m) ppm.                                                 336   122-124                                                                 337     97-98.5                                                               338   108-110                                                                 339   136-137                                                                 340   125-126                                                                 341   113-116                                                                 342   120-124                                                                 343   87-89                                                                   344   62-64                                                                   345   Gum   2.29(3H, s), 2.89(3H, d), 3.46(3H, s), 3.77(2H, t),                           3.96(3H, s), 4.19(2H, t), 5.16(2H, s), 6.76(1H, m),                           6.81(1H, dd), 7.2-7.5(5H, m), 8.39(1H, d) ppm.                    346*  114-116                                                                 347   87.4-88.4                                                               348   143.5-143.9                                                             349   111.6-112.8                                                             350   118.4-118.8                                                             __________________________________________________________________________     *Table III                                                               

The compounds of the invention can be prepared by the methods describedin EP-A-0370629 and EP-A-0398692. The former reference shows how toprepare similar compounds which have a methyl β-methoxyacrylate groupattached to the phenyl ring in formula I instead of an O-methyloxyiminoacetamide group. The latter reference shows how to construct theoxyiminoacetamide group.

The invention also includes a process for preparing a compound accordingto claim 1 which comprises reacting a compound of the formula (II) withan amine NHR⁵ R⁶, wherein A, R¹, R², R⁵ and R⁶ have the meanings givenabove, and R is H or C₁₋₄ alkyl.

Methyl 2-(bromomethyl)phenylglyoxylate O-methyloxime (compound A inScheme I under "Chemical Formulae" later) provides a convenient startingmaterial. It may be prepared, as described in EP-A-0363818, by thebromination of methyl 2-methylphenylglyoxylate O-methyloxime. The(E)-isomer of the latter compound, for use in preparing the preferred(E)-isomers of the compounds of formula (I), may be obtained from the(Z)-isomer or from a mixture of the (Z)- and (E)-isomers byisomerization under acidic conditions, for instance, as described inExample 2. Alternatively, the isomerization step may be performed as afinal step on the compound of formula (I).

The compounds are active fungicides and may be used to control one ormore of the following pathogens: Pyricularia oryzae on rice; Pucciniarecondita, Puccinia striiformis and other rusts on wheat, Pucciniahordei, Puccinia striiformis and other rusts on barley, and rusts onother hosts e.g. coffee, pears, apples, peanuts, vegetables andornamental plants; Erysiphe graminis (powdery mildew) on barley andwheat and other powdery mildews on various hosts such as Sphaerothecamacularis on hops, Sphaerotheca fuliginea on cucurbits (e.g. cucumber),Podosphaera leucotricha on apple and Uncinula necator on vines;Helminthosporium spp., Rhynchosporium spp., Septoria spp., Pyrenophoraspp., Pseudocercosporella herpotrichoides and Gaeumannomyces graminis oncereals; Cercospora arachidicola and Cercosporidium personata on peanutsand other Cercospora species on other hosts, for example, sugar beet,bananas, soya beans and rice; Botrytis cinerea (grey mould) on tomatoes,strawberries, vegetables, vines and other hosts; Alternaria spp. onvegetables (e.g. cucumber), oil-seed rape, apples, tomatoes and otherhosts; Venturia inaequalis (scab) on apples; Plasmopara viticola onvines; other downy mildews such as Bremia lactucae on lettuce,Peronospora spp. on soybeans, tobacco, onions and other hosts,Pseudoperonospora humuli on hops and Pseudoperonospora cubensis oncucurbits; Phytophthora infestans on potatoes and tomatoes and otherPhytophthora spp. on vegetables, strawberries, avocado, pepper,ornamentals, tobacco, cocoa and other hosts; Thanatephorus cucumeris onrice and other Rhizoctonia species on various hosts such as wheat andbarley, vegetables, cotton and turf.

Some of the compounds show a broad range of activities against fungi invitro. They may also have activity against various post-harvest diseasesof fruit (e.g. Penicillium digitatum and italicum and Trichoderma virideon oranges, Gloeosporium musarum on bananas and Botrytis cinerea ongrapes).

Further, some of the compounds may be active as seed dressings againstpathogens including Fusarium spp., Septoria spp., Tilletia spp., (bunt,a seed-borne disease of wheat), Ustilago spp. and Helminthosporium spp.on cereals, Rhizoctonia solani on cotton and Pyricularia oryzae on rice.

The compounds may move acropetally/locally in plant tissue. Moreover,the compounds may be volatile enough to be active in the vapour phaseagainst fungi on the plant.

The invention therefore provides a method of combating fungi whichcomprises applying to a plant, to a seed of a plant or to the locus ofthe plant or seed a fungicidally effective amount of a compound ashereinbefore defined, or a composition containing the same.

The compounds may be used directly for agricultural purposes but aremore conveniently formulated into compositions using a carrier ordiluent. The invention thus provides fungicidal compositions comprisinga compound as hereinbefore defined and an acceptable carrier or diluenttherefor.

The compounds can be applied in a number of ways. For example, they canbe applied, formulated or unformulated, directly to the foliage of aplant, to seeds or to other medium in which plants are growing or are tobe planted, or they can be sprayed on, dusted on or applied as a creamor paste formulation, or they can be applied as a vapour or as slowrelease granules.

Application can be to any part of the plant including the foliage,stems, branches or roots, or to soil surrounding the roots, or to theseed before it is planted, or to the soil generally, to paddy water orto hydroponic culture systems. The invention compounds may also beinjected into plants or sprayed onto vegetation using electrodynamicspraying techniques or other low volume methods.

The term "plant" as used herein includes seedlings, bushes and trees.Furthermore, the fungicidal method of the invention includespreventative, protectant, prophylactic and eradicant treatments.

The compounds are preferably used for agricultural and horticulturalpurposes in the form of a composition. The type of composition used inany instance will depend upon the particular purpose envisaged.

The compositions may be in the form of dustable powders or granulescomprising the active ingredient (invention compound) and a soliddiluent or carrier, for example, fillers such as kaolin, bentonite,kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia,fuller's earth, gypsum, diatomaceous earth and china clay. Such granulescan be preformed granules suitable for application to the soil withoutfurther treatment. These granules can be made either by impregnatingpellets of filler with the active ingredient or by pelleting a mixtureof the active ingredient and powdered filler. Compositions for dressingseed may include an agent (for example, a mineral oil) for assisting theadhesion of the composition to the seed; alternatively the activeingredient can be formulated for seed dressing purposes using an organicsolvent (for example, N-methylpyrrolidone, propylene glycol orN,N-dimethylformamide). The compositions may also be in the form ofwettable powders or water dispersible granules comprising wetting ordispersing agents to facilitate the dispersion in liquids. The powdersand granules may also contain fillers and suspending agents.

Emulsifiable concentrates or emulsions may be prepared by dissolving theactive ingredient in an organic solvent optionally containing a wettingor emulsifying agent and then adding the mixture to water which may alsocontain a wetting or emulsifying agent. Suitable organic solvents arearomatic solvents such as alkylbenzenes and alkylnaphthalenes, ketonessuch as cyclohexanone and methylcyclohexanone, chlorinated hydrocarbonssuch as chlorobenzene and trichlorethane, and alcohols such as benzylalcohol, furfuryl alcohol, butanol and glycol ethers.

Suspension concentrates of largely insoluble solids may be prepared byball or bead milling with a dispersing agent with a suspending agentincluded to stop the solid settling.

Compositions to be used as sprays may be in the form of aerosols whereinthe formulation is held in a container under pressure of a propellant,e.g. fluorotrichloromethane or dichlorodifluoromethane.

The invention compounds can be mixed in the dry state with a pyrotechnicmixture to form a composition suitable for generating in enclosed spacesa smoke containing the compounds.

Alternatively, the compounds may be used in micro-encapsulated form.They may also be formulated in biodegradable polymeric formulations toobtain a slow, controlled release of the active substance.

By including suitable additives, for example additives for improving thedistribution, adhesive power and resistance to rain on treated surfaces,the different compositions can be better adapted for various utilities.

The invention compounds can be used as mixtures with fertilisersnitrogen-, potassium- or phosphorus-containing fertilisers).Compositions comprising only granules of fertiliser incorporating, forexample coated with, the compound are preferred. Such granules suitablycontain up to 25% by weight of the compound. The invention thereforealso provides a fertiliser composition comprising a fertiliser and thecompound of general formula (I) or a salt or metal complex thereof.

Wettable powders, emulsifiable concentrates and suspension concentrateswill normally contain surfactants, e.g. a wetting agent, dispersingagent, emulsifying agent or suspending agent. These agents can becationic, anionic or non-ionic agents.

Suitable cationic agents are quaternary ammonium compounds, for example,cetyltrimethylammonium bromide. Suitable anionic agents are soaps, saltsof aliphatic monoesters of sulphuric acid (for example, sodium laurylsulphate), and salts of sulphonated aromatic compounds (for example,sodium dodecylbenzenesulphonate, sodium, calcium or ammoniumlignosulphonate, butylnaphthalene sulphonate, and a mixture of sodiumdiisopropyl- and triisopropylnaphthalene sulphonates).

Suitable non-ionic agents are the condensation products of ethyleneoxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkylphenols such as octyl- or nonylphenol and octylcresol. Other non-ionicagents are the partial esters derived from long chain fatty acids andhexitol anhydrides, the condensation products of the said partial esterswith ethylene oxide, and the lecithins. Suitable suspending agents arehydrophilic colloids (for example, polyvinylpyrrolidone and sodiumcarboxymethylcellulose), and swelling clays such as bentonite orattapulgite.

Compositions for use as aqueous dispersions or emulsions are generallysupplied in the form of a concentrate containing a high proportion ofthe active ingredient, the concentrate being diluted with water beforeuse. These concentrates should preferably be able to withstand storagefor prolonged periods and after such storage be capable of dilution withwater in order to form aqueous preparations which remain homogeneous fora sufficient time to enable them to be applied by conventional sprayequipment. The concentrates may conveniently contain up to 95%, suitably10-85%, for example 25-60%, by weight of the active ingredient. Afterdilution to form aqueous preparations, such preparations may containvarying amounts of the active ingredient depending upon the intendedpurpose, but an aqueous preparation containing 0.0005% or 0.01% to 10%by weight of active ingredient may be used.

The compositions of this invention may contain other compounds havingbiological activity, e.g. compounds having similar or complementaryfungicidal activity or which possess plant growth regulating, herbicidalor insecticidal activity.

A fungicidal compound which may be present in the composition of theinvention may be one which is capable of combating ear diseases ofcereals (e.g. wheat) such as Septoria, Gibberella and Helminthosporiumspp., seed and soil-borne diseases and downy and powdery mildews ongrapes and powdery mildew and scab on apple, etc. By including anotherfungicide, the composition can have a broader spectrum of activity thanthe compound of general formula (I) alone. Further the other fungicidecan have a synergistic effect on the fungicidal activity of the compoundof general formula (I). Examples of fungicidal compounds which may beincluded in the composition of the invention are(RS)-1-aminopropylphosphonic acid,(RS)-4-(4-chlorophenyl)-2-phenyl-2-(1H-1,2,4-triazol-1-ylmethyl)butyronitrile,(Z)-N-but-2-enyloxymethyl-2-chloro-2',6'-diethylacetanilide,1-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea,3-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl)quinazolin-4(3H)-one,4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-1-sulphonamide,5-ethyl-5,8-dihydro-8-oxo(1,3)-dioxol(4,5-g)quinoline-7-carboxylic acid,α-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-γ-butyrolactone,aldimorph, anilazine, benalaxyl, benomyl, biloxazol, binapacryl,bitertanol, blasticidin S, bromuconazole, bupirimate, buthiobate,captafol, captan, carbendazim, carboxin, chlorbenzthiazone, chloroneb,chlorothalonil, chlorozolinate, copper containing compounds such ascopper oxychloride, copper sulphate and Bordeaux mixture, cycloheximide,cymoxanil, cyproconazole, cyprofuram, di-2-pyridyl disulphide1,1'-dioxide, dichlofluanid, dichlone, diclobutrazol, diclomezine,dicloran, difenoconazole, dimethamorph, dimethirimol, diniconazole,dinocap, ditalimfos, dithianon, dodemorph, dodine, edifenphos,etaconazole, ethirimol, ethyl(Z)-N-benzyl-N-([methyl(methylthioethylideneamino-oxycarbonyl)amino]thio)-βalaninate,etridiazole, fenapanil, fenarimol, fenfuram, fenpiclonil, fenpropidin,fenpropimorph, fentin acetate, fentin hydroxide, flutolanil, flutriafol,flusilazole, folpet, fosetyl-aluminium, fuberidazole, furalaxyl,furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, imazalil,imibenconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin,mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, methfuroxam,metsulfovax, myclobutanil, neoasozin, nickel dimethyldithiocarbamate,nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds,oxadixyl, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazinoxide, phthalide, polyoxin D, polyram, probenazole, prochloraz,procymidone, propamocarb, propiconazole, propineb, prothiocarb,pyrazophos, pyrifenox, pyroquilon, pyroxyfur, pyrrolnitrin,quinomethionate, quintozene, SSF-109, streptomycin, sulphur,tebuconazole, techlofthalam, tecnazene, tetraconazole, thiabendazole,thicyofen, thiophanate-methyl, thiram, tolclofos-methyl, triacetate saltof 1,1'-iminodi(octamethylene)diguanidine, triadimefon, triadimenol,triazbutyl, tricyclazole, tridemorph, triforine, validamycin A,vinclozolin, zarilamid and zineb. The compounds of general formula (I)can be mixed with soil, peat or other rooting media for the protectionof plants against seed-borne, soil-borne or foliar fungal diseases.

Suitable insecticides which may be incorporated in the composition ofthe invention include buprofezin, carbaryl, carbofuran, carbosulfan,chlorpyrifos, cycloprothrin, demeton-s-methyl, diazinon, dimethoate,ethofenprox, fenitrothion, fenobucarb, fenthion, formothion, isoprocarb,isoxathion, monocrotophos, phenthoate, pirimicarb, propaphos and XMC.

Plant growth regulating compounds are compounds which control weeds orseedhead, formation, or selectively control the growth of less desirableplants (e.g. grasses).

Examples of suitable plant growth regulating compounds for use with theinvention compounds are 3,6-dichloropicolinic acid,1-(4-chlorophenyl)-4,6-di-methyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid, methyl-3,6-dichloroanisate, abscisic acid, asulam,benzoylprop-ethyl, carbetamide, daminozide, difenzoquat, dikegulac,ethephon, fenpentezol, fluoridamid, glyphosate, glyphosine,hydroxybenzonitriles (e.g. bromoxynil), inabenfide, isopyrimol, longchain fatty alcohols and acids, maleic hydrazide, mefluidide,morphactins (e.g. chlorfluoroecol), paclobutrazol, phenoxyacetic acids(e.g. 2,4-D or MCPA), substituted benzoic acid (e.g. triiodobenzoicacid), substituted quaternary ammonium and phosphonium compounds (e.g.chloromequat, chlorphonium or mepiquatchloride), tecnazene, the auxins(e.g. indoleacetic acid, indolebutyric acid, naphthylacetic acid ornaphthoxyacetic acid), the cytokinins (e.g. benzimidazole,benzyladenine, benzylaminopurine, diphenylurea or kinetin), thegibberellins (e.g. GA₃, GA₄ or GA₇) and triapenthenol.

The following Examples illustrate the invention. Throughout theExamples, the term `ether` refers to diethyl ether, magnesium sulphatewas used to dry solutions, except where otherwise stated, and solutionswere concentrated under reduced pressure. Reactions involving air- orwater-sensitive intermediates were performed under an atmosphere ofnitrogen and solvents were dried before use, where appropriate. Unlessotherwise stated, chromatography was performed on a column of silica gelas the stationary phase. Where shown, NMR data are selective; no attemptis made to list every absorption in all cases. ¹ H NMR spectra wererecorded using CDCl₃ solutions unless otherwise stated. The followingabbreviations are used throughout:

    ______________________________________                                        DMF =  .sub.--N, .sub.--N-dimethylformamide                                                          d = doublet                                            NMR = nuclear magnetic resonance                                                                     m = multiplet                                          s = single:            br = broad                                             ______________________________________                                    

EXAMPLE 1

This Example illustrates the preparation of compound No. 127 of Table I(see Scheme I).

A solution of 3-trifluoromethylacetophenone oxime (1.59 g) in DMF (20ml) was added dropwise to a stirred suspension of sodium hydride (0.187g) in DMF (10 ml). An hour later, the reaction mixture was cooled to 0°C. and a solution of (E)-methyl 2-(bromomethyl)phenylglyoxylateO-methyloxime [(A), 2.36 g, prepared as described in EP-A-0363818]in DMF(20 ml) was added dropwise with stirring. After a further 3 hours, thereaction mixture was poured into water and extracted with ethyl acetate(×3). The organic extracts were washed with brine, dried, concentratedand chromatographed using ethyl acetate:hexane (1:4) as eluant to givethe bis-oxime ether (B) (2.83 g, 88% yield) as a colourless gum; ¹ H NMR(270 MHz): δ2.21(3H,s), 3.82(3H,s), 4.03(3H,s), 5.15(2H,s),7.1-7.9(8H,m) ppm.

A solution of the bis-oxime ether (B) (2.3 g) in methanol was addeddropwise to a cooled, saturated solution of methylamine in methanol (200ml). After standing for 2 days, the reaction mixture was concentratedand the residual yellow gum was chromatographed using ether:hexane (3:2)as eluant to give the title compound (1.46 g, 64% yield) as a clear gum;¹ H NMR (270 MHz): δ2.22 (3H,s), 2.88(3H,d), 3.94(3H,s), 5.14(2H,s),6.74(1H,br m), 7.1-7.9(8H,m) ppm.

EXAMPLE 2

This Example illustrates the isomerization of (Z)-methyl2-methylphenylglyoxylate O-methyloxime to the corresponding (E)-isomerfor use in the preparation of (E)-methyl 2-(bromomethyl)phenylglyoxylateO-methyloxime (A) in Example 1.

(Z)-Methyl 2-methylphenylglyoxylate O-methyloxime (102 mg) was dissolvedin dioxane (5 ml) and concentrated hydrochloric acid (0.25 ml) wasadded. The reaction was heated to reflux for 24 hours and allowed tocool. The reaction was partitioned between ether and a saturatedsolution of sodium bicarbonate in water. The aqueous layer was extractedtwice more with ether and the combined organic layers were dried (sodiumsulphate) and concentrated. The residue was purified by flashchromatography (eluting with 25% ether in hexane) to give the titlecompound (42 mg, 41% yield); ¹ H NMR (270 MHz): δ2.2(3H,s), 3.85(3H,s),4.05(3H,s), 7.1(1H,m), 7.2-7.4(3H,m) ppm.

The following are examples of compositions suitable for agricultural andhorticultural purposes which can be formulated from the compounds of theinvention. Such compositions form another aspect of the invention.

EXAMPLE 3

An emulsifiable concentrate is made up by mixing and stirring theingredients until all are dissolved.

    ______________________________________                                        Compound No. 260 of Table I                                                                              10%                                                Benzyl alcohol             30%                                                Calcium dodecylbenzenesulphonate                                                                          5%                                                NonylphenolethoxyIate (13 mole ethylene oxide)                                                           10%                                                Alkyl benzenes             45%                                                ______________________________________                                    

EXAMPLE 4

The active ingredient is dissolved in methylene dichloride and theresultant liquid sprayed on to the granules of attapulgite clay. Thesolvent is then allowed to evaporate to produce a granular composition.

    ______________________________________                                        Compound No. 264 of Table I                                                                         5%                                                      Attapulgite granules 95%                                                      ______________________________________                                    

EXAMPLE 5

A composition suitable for use as a seed dressing is prepared bygrinding and mixing the three ingredients.

    ______________________________________                                        Compound No. 269 of Table I                                                                        50%                                                      Mineral oil           2%                                                      China clay           48%                                                      ______________________________________                                    

EXAMPLE 6

A dustable powder is prepared by grinding and mixing the activeingredient with talc.

    ______________________________________                                        Compound No. 295 of Table I                                                                         5%                                                      Talc                 95%                                                      ______________________________________                                    

EXAMPLE 7

A suspension concentrate is prepared by ball milling the ingredients toform an aqueous suspension of the ground mixture with water.

    ______________________________________                                        Compound No. 330 of Table I                                                                        40%                                                      Sodium lignosulphonate                                                                             10%                                                      Bentonite clay        1%                                                      Water                49%                                                      ______________________________________                                    

This formulation can be used as a spray by diluting into water orapplied directly to seed.

EXAMPLE 8

A wettable powder formulation is made by mixing together and grindingthe ingredients until all are thoroughly mixed.

    ______________________________________                                        Compound No. 331 of Table I                                                                        25%                                                      Sodium lauryl sulphate                                                                              2%                                                      Sodium lignosulphonate                                                                              5%                                                      Silica               25%                                                      China clay           43%                                                      ______________________________________                                    

EXAMPLE 9

The compounds were tested against a variety of foliar fungal diseases ofplants. The technique employed was as follows.

The plants were grown in John Innes Potting Compost (No. 1 or 2) in 4 cmdiameter minipots. The test compounds were formulated either by beadmilling with aqueous Dispersol T or as a solution in acetone oracetone/ethanol which was diluted to the required concentrationimmediately before use. The formulations (100 ppm active ingredient)were sprayed on to the foliage or applied to the roots of the plants inthe soil. The sprays were applied to maximum retention and the rootdrenches to a final concentration equivalent to approximately 40 ppma.i. in dry soil. Tween 20 was added to give a final concentration of0.05% when the sprays were applied to cereals.

For most of the tests the compounds were applied to the soil (roots) orto the foliage (by spraying) one or two days before the plant wasinoculated with the disease. Exceptions were the tests on Pucciniarecondita and on Erysiphe graminis in which the plants were inoculated48 hours and 24 hours, respectively, before treatment. Foliar pathogenswere applied by spray as zoosporangial suspensions onto the leaves oftest plants. After inoculation, the plants were put into an appropriateenvironment to allow infection to proceed and then incubated until thedisease was ready for assessment. The period between inoculation andassessment varied from four to fourteen days according to the diseaseand environment.

The disease level present (i.e. leaf area covered by activelysporulating disease) on each of the treated plants was recorded usingthe following assessment scale:

    ______________________________________                                                0 = 0% disease present                                                        1 = 0.1-1% disease present                                                    3 = 1.1-3% disease present                                                    5 = 3.1-5% disease present                                                   10 = 5.1-10 disease present                                                   20 = 10.1-20% disease present                                                 30 = 20.1-30% disease present                                                 60 = 30.1-60% disease present                                                 90 = 60.1-100% disease present                                         ______________________________________                                    

Each assessment was then expressed as a percentage of the level ofdisease present on the untreated control plants. This calculated valueis referred to as a POCO (Percentage of Control) value. An example of atypical calculation is as follows:

Disease level on untreated control=90

Disease level on treated plant=30 ##EQU1##

This calculated POCO value is then rounded to the nearest of the valuesin the 9-point assessment scale shown above. In this particular example,the POCO value would be rounded to 30. If the calculated POCO fallsexactly mid-way between two of the points, it is rounded to the lower ofthe two values.

The results displayed in Table V below represent these rounded POCOvalues.

                  TABLE V                                                         ______________________________________                                        Compound                                                                      No of Table I                                                                           Pr    Egt     Sn  Po    Tc  Vi   Pv  Pil                            ______________________________________                                         63       0     0       0   10    --  0    0   30                              75       .sup. 0.sup.a                                                                       .sup. 0.sup.a                                                                         .sup. 5.sup.a                                                                     90.sup.a                                                                            --  .sup. 0.sup.a                                                                      .sup. 0.sup.a                                                                     .sup. 90.sup.a                 103       .sup. 5.sup.a                                                                       30.sup.a                                                                              .sup. 1.sup.a                                                                     20.sup.a                                                                            --  .sup. 0.sup.a                                                                      .sup. 0.sup.a                                                                     .sup. 90.sup.a                 109       .sup. 1.sup.a                                                                       .sup. 0.sup.a                                                                         .sup. 0.sup.a                                                                     .sup. 0.sup.a                                                                       --  .sup. 0.sup.a                                                                      .sup. 0.sup.a                                                                     .sup. 90.sup.a                 115       0     0       0   0     --  0    0    0                             127        0*   0       0   0     0   0    0    0                             176       0     0       0   1     --  0    0    0                             236       0     0       0   0     0   0    0   10                             260        0*   0       0   0     0   0    0    3                             269        0*   0       0   0     5   0    0    5                             326       0     0       0   0     --  0    0    0                             328       0     0       0   0     0   0    0   90                             329       .sup. 5.sup.a                                                                       30.sup.a                                                                              .sup. 3.sup.a                                                                     20.sup.a                                                                            --  .sup. 0.sup.a                                                                      .sup. 0.sup.a                      331       .sup. 5.sup.a                                                                       .sup. 0.sup.a                                                                         30.sup.a                                                                          90.sup.a                                                                            --  20.sup.a                                                                           10.sup.a                                                                          .sup. 90.sup.a                 332       .sup. 5.sup.a                                                                       .sup. 0.sup.a                                                                         .sup. 5.sup.a                                                                     30.sup.a                                                                            --  .sup. 0.sup.a                                                                      .sup. 0.sup.a                                                                     .sup. 90.sup.a                 333       0     0       0   20    --  0    0   90                             334       10.sup.a                                                                            30.sup.a                                                                              20.sup.a                                                                          30.sup.a                                                                            --  60.sup.a                                                                           10.sup.a                                                                          .sup. 90.sup.a                 335       .sup. 5.sup.a                                                                       .sup. 0.sup.a                                                                         30.sup.a                                                                          90.sup.a                                                                            --  .sup. 5.sup.a                                                                      .sup. 5.sup.a                                                                     .sup. 90.sup.a                 .sup.   335A                                                                            0     0       0   0     --  0    0   10                             336       0     0       0   30    --  0    0   90                             337       0     0       0   0     0   0    0   10                             ______________________________________                                         .sup.a 10 ppm foliar application only                                         *foliar protectant test (i.e. pant inoculated before treatment)               -- = No result                                                                Key to diseases                                                               Pr Puccinia recondita                                                         Egt Erysiphe graminis tritici                                                 Sn Septoria nodorum                                                           Po Pyricularia oryzae                                                         Tc Thanetophorus cucumeris                                                    Vi Venturia inaequalis                                                        Pv Plasmopara viIiccla                                                        Pil Phytophthora infestans lycopersici                                   

CHEMICAL FORMULAE (in description) ##STR2##

                  TABLE I                                                         ______________________________________                                                                      (I.1)                                           ______________________________________                                    

                  TABLE II                                                        ______________________________________                                         ##STR3##                     (I.2)                                           ______________________________________                                    

                  TABLE III                                                       ______________________________________                                         ##STR4##                     (I.3)                                           ______________________________________                                    

Compound 53 is ##STR5## Compound 54 is ##STR6## Compound 55 is ##STR7##Compound 152 is ##STR8## Compound 153 is ##STR9## Compound 307 is##STR10## Compound 318 is ##STR11## Compound 325 is ##STR12##

We claim:
 1. A compound having the formula (I):and stereoisomersthereof, wherein A is hydrogen, halo, hydroxy, C₁₋₄ alkyl, C₁₋₄ alkoxy,C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, C₁₋₄ alkylcarbonyl, C₁₋₄alkoxycarbonyl, phenoxy, nitro or cyano; R¹ is an optionally substitutedsix-membered heterocycle containing two nitrogen atoms; R² is hydrogen,optionally substituted alkyl, optionally substituted cycloalkyl,optionally substituted cycloalkylalkyl, optionally substituted aralkyl,optionally substituted aryloxyalkyl, optionally substituted alkenyl,optionally substituted alkynyl, optionally substituted alkoxy,optionally substituted aryl optionally substituted aryloxy, nitro, halo,cyano, --NR³ R⁴, --CO₂ R³, --CONR³ R⁴, --COR³, --S(O)_(n) R³ wherein nis 0, 1 or 2, or (CH₂)_(m) PO(OR³)₂, wherein m is 0 or 1, R³ and R⁴,which are the same or different, are hydrogen, optionally substitutedalkyl, optionally substituted aralkyl, optionally substituted alkenyl,optionally substituted alkynyl, or optionally substituted aryl; and R⁵and R⁶ are independently hydrogen or C₁₋₄ alkyl.
 2. A compound accordingto claim 1 wherein alkyl and alkoxy moieties are optionally substitutedwith halo, cyano, hydroxy, C₁₋₄ alkoxy or C₁₋₄ alkoxy(C₁₋₄)alkoxy;cycloalkyl moieties are optionally substituted with halo, hydroxy orC₁₋₄ alkoxy; alkenyl moieties are optionally substituted with optionallysubstituted aryl; alkynyl moieties are optionally substituted withoptionally substituted aryl; and aryl and heterocycle moieties areoptionally substituted with one or more of the following: halo, hydroxy,mercapto, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄ alkoxy, C₂₋₄alkenyloxy, C₂₋₄ alkenyloxy, C₂₋₄ alkynyloxy, halo(C₁₋₄)alkyl,halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, hydroxy(C₁₋₄)alkyl, C₁₋₄alkoxy(C₁₋₄)alkyl, C₁₋₄ alkoxy(C₁₋₄)alkoxy, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl, optionally substituted aryl, optionallysubstituted aryloxy, optionally substituted aryl(C₁₋₄)alkyl, in whichthe alkyl moiety is optionally substituted with hydroxy, optionallysubstituted aryl(C₂₋₄)alkenyl, optionally substituted aryl(C₁₋₄)alkoxy,optionally substituted aryloxy(C₁₋₄)alkyl, acyloxy, cyano, isocyano,thiocyanato, isothiocyanato, nitro, --NR'R", --NHCOR', --NHCONR'R",--CONR'R", --COOR', --OSO₂ R', --SO₂ R", --COR', --CR'═NR" or --N═CR'R'in which R' and R"are independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy,C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl orbenzyl, these phenyl and benzyl groups being optionally substituted withhalogen, C₁₋₄ alkyl or C₁₋₄ alkoxy; and the aryl rings of any of theother foregoing substituents being optionally substituted with one ormore of the following: halo, hydroxy, mercapto, C₁₋₄ alkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, C₁₋₄ alkoxy, C₂₋₄ alkenyloxy, C₂₋₄ alkynyloxy,halo(C₁₋₄)alkyl, halo(C₁₋₄)alkoxy C₁₋₄ alkylthio, hydroxy(C₁₋₄)alkyl,C₁₋₄ alkoxy(C₁₋₄)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl,alkanoyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato,nitro, --NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --SO₂ R',--OSO₂ R', --COR', --CR'═NR" or --N═CR'R" in which R' and R' have themeanings given above.
 3. A compound according to claim 1 in whichheterocyclyl moieties are selected from the group consisting ofpyrimidinyl, pyrazinyl, and pyridazinyl groups and, where appropriate,N-oxides thereof.
 4. A compound according to claim 1 wherein A ishydrogen or halo; R¹ is pyrimidinyl, pyrazinyl, or pyridazinyl, any ofthe foregoing being optionally substituted with one or more of halo,C₁₋₄ alkyl, trifluoromethyl, C₁₋₄ alkoxy, trifluoromethoxy, nitro,cyano, phenyl or benzyloxy; and R² is hydrogen, C₁₋₄ alkyl, C₁₋₄alkylcarbonyl, C₁₋₄ alkoxycarbonyl cyano or phenyl.
 5. A compoundaccording to claim 1 wherein A is hydrogen; R¹ is pyrimidinyl,pyrazinyl, or pyridazinyl, any of the foregoing being optionallysubstituted with one or more of halo, C₁₋₆ alkyl, halo(C₁₋₄)alkyl, C₁₋₆alkoxy, cyano(C₁₋₄)alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkoxy(C₁₋₄)alkyl,C₁₋₄ alkoxy(C₁₋₄)alkloxy, C₁₋₄ alkoxy(C₁₋₄ alkoxy(C₁₋₄)alkoxy, C₁₋₆alkylthio, C₂₋₆ alkenyl, C₂₋₆ alkenyloxy, C₂₋₆ alkynyl, C₂₋₆ alkynyloxy,nitro, cyano, phenyl, phenoxy, benzyloxy, CO₂ R', CONR'R", CSNR'R",NR'R", S(O)_(n) R', NHCONR'R", in which R' and R" are independently H orC₁₋₄ alkyl and n is 0, 1 or 2; R² is methyl; R⁵ is hydrogen and R⁶ ismethyl; or where appropriate, the N-oxide thereof.
 6. A compound inaccordance with claim 1 herein R¹ is optionally substituted pyrimidinyl.7. A compound in accordance with claim 4 wherein R¹ is pyrimidinyl.
 8. Acompound in accordance with claim 5 wherein R¹ is pyrimidinyl.
 9. Afungicidal composition comprising, as an active ingredient, afungicidally effective amount of a compound as defined in claim 1 and afungicidally acceptable carrier or diluent therefor.
 10. A method forcombating fungi which comprises applying to plants or seeds, or to theirlocus, a fungicidally effective amount of a compound as claimed in claim1.